May 21, 2024

Protein Activation in the Brain May Offer Protection Against Alzheimer’s in Women

A recent study conducted at the Karolinska Institute has revealed that the activation of a specific brain protein may provide protection against neurodegenerative diseases, such as Alzheimer’s disease, in women.

The research, led by Silvia Maioli, an Associate Professor at the Department of Neurobiology, Care Sciences and Society at Karolinska Institutet, suggests that cholesterol turnover and sex hormones are factors that can be modified and potentially serve as treatment targets for various neurodegenerative diseases in the future.

The study, which was carried out on mice, focused on the brain protein CYP46A1 and its role in protecting women from neurodegenerative diseases. CYP46A1 is responsible for converting excess cholesterol in the brain into a cholesterol product called 24S-hydroxycholesterol (24OH). By increasing the levels of this protein in the mice, the researchers observed positive effects in females, including improved memory capacities, healthier neurons, and higher estrogen activity during menopause-like conditions and aging. These effects were not seen in male mice.

Furthermore, measurements of 24OH in the cerebrospinal fluid of Alzheimer’s disease patients indicated that higher levels of 24OH correlated with lower levels of Alzheimer’s markers, such as tau, but only in women.

It is worth noting that two-thirds of individuals diagnosed with Alzheimer’s disease are women, and early menopause is a specific risk factor for cognitive decline. Estrogen, a hormone vital for maintaining healthy and functional neurons, is produced not only in the ovaries but also in the brain. Therefore, the activation of CYP46A1, which increases estrogen activity in the brains of menopausal and elderly female mice, suggests that this protein could be a potential therapeutic target specific to women.

Previous research has demonstrated that CYP46A1 can be activated pharmacologically using low doses of the anti-HIV drug Efavirenz. This finding opens up the possibility of targeting cholesterol metabolism through CYP46A1 activators like Efavirenz as a new approach to promote estrogen-mediated neuroprotection in women at risk of developing Alzheimer’s disease.

The study’s findings could have significant implications for the future treatment and prevention of Alzheimer’s disease, particularly in women. Further research is necessary to explore the potential clinical applications of these findings and to determine if the activation of CYP46A1 can provide similar benefits in human subjects. Nonetheless, this study represents a promising step forward in understanding the mechanisms behind neurodegenerative diseases and developing gender-specific therapeutic strategies.

1. Source: Coherent Market Insights, Public sources, Desk research
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